Breast-Feeding and Childhood-Onset Type 1 Diabetes
A pooled analysis of individual participant data from 43 observational studies
- Chris R. Cardwell, PHD1⇓,
- Lars C. Stene, PHD2,3,
- Johnny Ludvigsson, MD, PHD4,
- Joachim Rosenbauer, MD, DIPL MATH5,
- Ondrej Cinek, MD, PHD6,
- Jannet Svensson, PHD7,
- Francisco Perez-Bravo, PHD8,
- Anjum Memon, MBBS, DPHIL9,
- Suely G. Gimeno, DPH10,
- Emma J.K. Wadsworth, PHD11,
- Elsa S. Strotmeyer, PHD12,
- Michael J. Goldacre, FFPHM13,
- Katja Radon, PHD14,
- Lee-Ming Chuang, MD, PHD15,
- Roger C. Parslow, PHD16,
- Amanda Chetwynd, PHD17,
- Kyriaki Karavanaki, MD, PHD18,
- Girts Brigis, MD, PHD19,
- Paolo Pozzilli, MBBS, MD20,
- Brone UrbonaitĖ, MD, PHD21,
- Edith Schober, MD22,
- Gabriele Devoti, MD23,
- Sandra Sipetic, MD, PHD24,
- Geir Joner, MD, PHD25,26,
- Constantin Ionescu-Tirgoviste, MD, PHD27,
- Carine E. de Beaufort, MD, PHD28,
- Kirsten Harrild, MSC29,
- Victoria Benson, PHD30,
- Erkki Savilahti, MD, PHD31,
- Anne-Louise Ponsonby, MBBS, PHD32,
- Mona Salem, MD33,
- Samira Rabiei, MSC34 and
- Chris C. Patterson, PHD1
- 1School of Medicine and Dentistry, Queen’s University Belfast, Belfast, U.K.
- 2Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway
- 3Oslo Diabetes Research Centre, Oslo University Hospital, Oslo, Norway
- 4Department of Clinical Experimental Medicine, Division of Pediatrics, Linkoping University Hospital, Linkoping, Sweden
- 5Institute of Biometrics and Epidemiology, German Diabetes Centre, Leibniz Institute at Duesseldorf University, Duesseldorf, Germany
- 6Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Motol, Czech Republic
- 7Pediatric Department, Herlev University Hospital, Herlev, Denmark
- 8Department of Nutrition, Faculty of Medicine, Laboratory of Nutritional Genomics, University of Chile, Santiago, Chile
- 9Division of Primary Care and Public Health, Brighton and Sussex Medical School and NHS Brighton and Hove, Brighton, U.K.
- 10Preventive Medicine Department, Federal University of São Paulo, São Paulo, Brazil
- 11Cardiff Work Environment Research Centre, Cardiff University, Cardiff, U.K.
- 12Department of Epidemiology, Graduate School of Public Health, Center for Aging and Population Health, University of Pittsburgh, Pittsburgh, Pennsylvania
- 13Department of Public Health, Oxford University, Oxford, U.K.
- 14Institute and Outpatient Clinic for Occupational and Environmental Medicine, Hospital of the Ludwig Maximilian University Munich, Munich, Germany
- 15Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- 16Paediatric Epidemiology Group, University of Leeds, Leeds, U.K.
- 17Mathematics and Statistics Department, Lancaster University, Lancaster, U.K.
- 18Second University Department of Pediatrics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
- 19Department of Public Health and Epidemiology, Riga Stradins University, Riga, Latvia
- 20University Campus Bio-Medico, Rome, Italy
- 21Institute of Endocrinology of Lithuanian University of Health Science, Kaunas, Lithuania
- 22Department of Paediatrics, Medical University of Vienna, Vienna, Austria
- 23Department of Social Sciences and Communication, University of Salento, Lecce, Italy
- 24School of Medicine, Institute of Epidemiology, Belgrade University, Belgrade, Serbia
- 25Faculty of Medicine, Institute of Health and Society, University of Oslo, Oslo, Norway
- 26Department of Paediatrics, Oslo University Hospital, Oslo, Norway
- 27Nutrition and Metabolic Diseases Clinic, N. Paulescu Institute of Diabetes, Bucharest, Romania
- 28Clinique Pédiatrique Luxembourg, Luxembourg City, Luxembourg
- 29Medical Statistics Team, University of Aberdeen, Aberdeen, U.K.
- 30Cancer Epidemiology Unit, University of Oxford, Oxford, U.K.
- 31Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
- 32Murdoch Children’s Research Institute, The Royal Children’s Hospital, Melbourne, Australia
- 33Paediatrics Department, Ain Shams University, Cairo, Egypt
- 34Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences and Health Services, Tehran, Iran
- Corresponding author: Chris R. Cardwell, .
OBJECTIVE To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders.
RESEARCH DESIGN AND METHODS Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies.
RESULTS Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64–0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75–1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81–1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78–1.00). These associations were all subject to marked heterogeneity (I2 = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75–0.99), and heterogeneity was reduced (I2 = 0%). Adjustments for potential confounders altered these estimates very little.
CONCLUSIONS The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc12-0438/-/DC1.
- Received March 5, 2012.
- Accepted May 9, 2012.
- © 2012 by the American Diabetes Association.
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